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Current Opinion in Organ Transplantation Apr 2023The shortage of donor organs has led to the use of marginal extended criteria donor (ECD) livers to increase access to liver transplant. Ex-vivo machine perfusion allows... (Review)
Review
PURPOSE OF REVIEW
The shortage of donor organs has led to the use of marginal extended criteria donor (ECD) livers to increase access to liver transplant. Ex-vivo machine perfusion allows for treatment and assessment of organs during preservation, potentially facilitating safe use of ECD livers at risk for worse clinical outcomes. This article reviews the latest published literature on the application of ex-vivo machine perfusion technologies in liver transplantation.
RECENT FINDINGS
Multiple randomized controlled trials on the use of hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) have been published in the past 5 years demonstrating improved graft function and decreased biliary complications after machine perfusion. Novel applications of machine perfusion include pretransplant organ viability testing, expansion to pediatric transplant, and prolonged preservation.
SUMMARY
There is now a body of evidence that HMP and NMP treatment improves clinical outcomes in ECD livers. There is a wide horizon for future applications of these preservation techniques to further optimize donor livers and to facilitate more liver transplants for those on the waitlist.
Topics: Humans; Child; Liver Transplantation; Organ Preservation; Living Donors; Perfusion; Liver
PubMed: 36752282
DOI: 10.1097/MOT.0000000000001054 -
Current Opinion in Organ Transplantation Feb 2020To summarise recently published studies of donor pretreatment and machine perfusion strategies in kidney transplantation. (Review)
Review
PURPOSE OF REVIEW
To summarise recently published studies of donor pretreatment and machine perfusion strategies in kidney transplantation.
RECENT FINDINGS
The sparsity of donor pretreatment trials has resulted in the re-analysis of already existing data, and RCTs are urgently needed to reinvigorate this aspect of donor research. Uncontrolled donation after circulatory death kidney transplantation has the highest risk of delayed graft function and graft failure, and recent studies have reported that normothermic regional perfusion improves graft function and survival in this setting. Hypothermic machine perfusion reduces delayed graft function following deceased donor kidney transplantation across donor types but unanswered questions still remain regarding its use. The use of oxygenated hypothermic machine perfusion appears to improve graft function in controlled donation after circulatory death mediated by a reduction in acute rejection. Ex-situ normothermic perfusion is emerging and while technically challenging it may facilitate the delivery of pretreatments.
SUMMARY
RCTs are urgently needed to reinvigorate research into donor pretreatment and to establish the place of specific preservation techniques in deceased donor kidney transplantation.
Topics: Humans; Organ Preservation; Organ Transplantation; Perfusion; Tissue Donors
PubMed: 31834008
DOI: 10.1097/MOT.0000000000000725 -
International Journal of Medical... 2021Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver... (Review)
Review
Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver transplantation and the shortage of donor pool restricts the development of liver transplantation. How to expand the donor pool is a significant problem to be solved clinically. Many doctors have devoted themselves to marginal grafting, which introduces livers with barely passable quality but a high risk of transplant failure into the donor pool. However, existing common methods of preserving marginal grafts lead to both high risk of postoperative complications and high mortality. The application of machine perfusion allows surgeons to make marginal livers meet the standard criteria for transplant, which shows promising prospect in preserving and repairing donor livers and improving ischemia reperfusion injury. This review summarizes the progress of recent researches on hepatic machine perfusion.
Topics: Humans; Liver Transplantation; Organ Preservation; Perfusion; Reperfusion Injury; Tissue and Organ Harvesting
PubMed: 33850464
DOI: 10.7150/ijms.56139 -
Mammalian Genome : Official Journal of... Sep 2022Tissue organoids or "mini organs" can be invaluable tools for understanding health and disease biology, modeling tissue dynamics, or screening potential drug candidates.... (Review)
Review
Tissue organoids or "mini organs" can be invaluable tools for understanding health and disease biology, modeling tissue dynamics, or screening potential drug candidates. Effective vascularization of these models is critical for truly representing the in vivo tissue environment. Not only is the formation of a vascular network, and ultimately a microcirculation, essential for proper distribution and exchange of oxygen and nutrients throughout larger organoids, but vascular cells dynamically communicate with other cells to modulate overall tissue behavior. Additionally, interstitial fluid flow, mediated by a perfused microvasculature, can have profound influences on tissue biology. Thus, a truly functionally and biologically relevant organoid requires a vasculature. Here, we review existing strategies for fabricating and incorporating vascular elements and perfusion within tissue organoids.
Topics: Organoids; Oxygen; Perfusion
PubMed: 35333952
DOI: 10.1007/s00335-022-09951-2 -
Advanced Healthcare Materials May 2021Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of...
Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of the native microvasculature. Multiphoton ablation has emerged as a promising technique for fabrication of microvascular structures with high resolution and full 3D control, but cellularization and perfusion of complex capillary-scale structures has remained challenging. Here, multiphoton ablation combined with guided endothelial cell growth from pre-formed microvessels is used to successfully create perfusable and cellularized organ-specific microvascular structures at anatomic scale within collagen hydrogels. Fabrication and perfusion of model 3D pulmonary and renal microvascular beds is demonstrated, as is replication and perfusion of a brain microvascular unit derived from in vivo data. Successful endothelialization and blood perfusion of a kidney-specific microvascular structure is achieved, using laser-guided angiogenesis. Finally, proof-of-concept hierarchical blood vessels and complex multicellular models are created, using multistep patterning with multiphoton ablation techniques. These successes open new doors for the creation of engineered tissues and organ-on-a-chip devices.
Topics: Ablation Techniques; Endothelial Cells; Humans; Microvessels; Perfusion; Tissue Engineering; Veins
PubMed: 33586357
DOI: 10.1002/adhm.202100031 -
Artificial Organs Feb 2022Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still... (Review)
Review
INTRODUCTION
Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still underexplored. This review aimed to examine the costs related to machine perfusion and its associated outcomes.
METHODS
Expert opinion of several groups representing different machine perfusion modalities. Critical analysis of the published literature reporting the economic outcomes of the most used techniques of machine perfusion in liver transplantation (normothermic and hypothermic ex situ machine perfusion and in situ normothermic regional perfusion).
RESULTS
Machine perfusion costs include disposable components of the perfusion device, perfusate components, personnel and facility fees, and depreciation of the perfusion device or device lease fee. The limited current literature suggests that although this upfront cost varies between perfusion modalities, its use is highly likely to be cost-effective. Optimization of the donor liver utilization rate, local conditions of transplant programs (long waiting list times and higher MELD scores), a decreased rate of complications, changes in logistics, and length of hospital stay are potential cost savings points that must highlight the expected benefits of this intervention. An additional unaccounted factor is that machine perfusion optimizing donor organ utilization allows patients to be transplanted earlier, avoiding clinical deterioration while on the waiting list and the costs associated with hospital admissions and other required procedures.
CONCLUSION
So far, the clinical benefits have guided machine perfusion implementation in liver transplantation. Albeit there is data suggesting the economic benefit of the technique, further investigation of its costs to healthcare systems and society and associated outcomes is needed.
Topics: Cost-Benefit Analysis; Humans; Liver Transplantation; Perfusion; Tissue and Organ Procurement
PubMed: 34878658
DOI: 10.1111/aor.14131 -
Transplantation Jan 2024Normothermic machine perfusion (NMP) aims to preserve organs ex vivo by simulating physiological conditions such as body temperature. Recent advancements in NMP system... (Review)
Review
Normothermic machine perfusion (NMP) aims to preserve organs ex vivo by simulating physiological conditions such as body temperature. Recent advancements in NMP system design have prompted the development of clinically effective devices for liver, heart, lung, and kidney transplantation that preserve organs for several hours/up to 1 d. In preclinical studies, adjustments to circuit structure, perfusate composition, and automatic supervision have extended perfusion times up to 1 wk of preservation. Emerging NMP platforms for ex vivo preservation of the pancreas, intestine, uterus, ovary, and vascularized composite allografts represent exciting prospects. Thus, NMP may become a valuable tool in transplantation and provide significant advantages to biomedical research. This review recaps recent NMP research, including discussions of devices in clinical trials, innovative preclinical systems for extended preservation, and platforms developed for other organs. We will also discuss NMP strategies using a global approach while focusing on technical specifications and preservation times.
Topics: Female; Humans; Organ Preservation; Kidney Transplantation; Liver; Perfusion; Liver Transplantation
PubMed: 37026713
DOI: 10.1097/TP.0000000000004573 -
Surgery Today Mar 2022In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver... (Review)
Review
In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver transplantation, organ preservation methods have so far changed very little. Static cold storage is universally used for graft preservation in liver transplantation; however, there is a need for better preservation methods, such as ex vivo machine perfusion, to improve the outcomes by decreasing warm ischemic damage. Based on the findings of basic and clinical trials, hypothermic and normothermic machine perfusion techniques are now commercially available and include the OrganOx metra, Liver Assist, Cleveland NMP device, Organ Care System, and LifePort Liver. Recent clinical trials have provided further evidence for the potential role of normothermic machine perfusion to resuscitate and subsequently improve utilization of marginal or currently discarded livers. Further studies are required to explore the longer-term outcomes, late biliary complications, outcomes in specific high-risk groups, viability biomarkers, optimum and maximum perfusion duration, perfusate composition, and liver-directed therapeutic interventions during normothermic machine perfusion. The use of organs from marginal donors after brain death, such as fatty livers and the livers from elderly donors with multiple comorbidities, may be accepted for machine perfusion in Japan in the near future.
Topics: Aged; Humans; Japan; Liver; Liver Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 33754175
DOI: 10.1007/s00595-021-02265-x -
Orvosi Hetilap Jul 2019In the last decades, the results of liver transplantation have shown significant improvement. More patients are eligible for liver transplantation, while the indications... (Review)
Review
In the last decades, the results of liver transplantation have shown significant improvement. More patients are eligible for liver transplantation, while the indications are changing. The worldwide shortage of donor organs urges the profession for the development of new strategies. With rational extension of donor criteria, more precise organ allocation, personalized donation, living related donation, machine perfusion, and donation after cardiac death, liver transplantation is becoming available for more and more patients suffering from end stage liver disease. Hereby we summarize the new possibilities and challenges in the light of the Hungarian liver transplant program. Orv Hetil. 2019; 160(29): 1127-1135.
Topics: Death; Donor Selection; Humans; Hungary; Liver Neoplasms; Liver Transplantation; Perfusion; Tissue Donors; Tissue and Organ Procurement
PubMed: 31303016
DOI: 10.1556/650.2019.31465 -
Transplantation Proceedings Nov 2021Most kidney grafts are marginal and from deceased donors, which yield worse clinical outcomes. Hypothermic machine perfusion has created a paradigm shift in kidney... (Review)
Review
Most kidney grafts are marginal and from deceased donors, which yield worse clinical outcomes. Hypothermic machine perfusion has created a paradigm shift in kidney preservation. This mini-review summarizes the main points of hypothermic machine perfusion of kidney transplants that should be known by any physician and surgeon involved with kidney transplantation. Specifically, this review explains a proposed mechanism of action of hypothermic machine perfusion of kidney transplants. This review also describes the clinical effectiveness of hypothermic machine perfusion and explains how to evaluate and predict graft functionality according to machine parameters and perfusate biomarkers. Finally, treatment options and the most recent studies on oxygenated hypothermic machine perfusion are mentioned.
Topics: Humans; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 34696905
DOI: 10.1016/j.transproceed.2021.09.011